Incidental 68Ga-DOTATATE uptake in the pancreatic head: A case report and a unique opportunity to improve clinical care.

RATIONALE: Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited by SSTR-based imaging such as In octreotide scintigraphy and Ga DOTATATE positron emission tomography (PET)/computed tomography (CT), which are considered standard for initial evaluation of NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of "false-positive" physiologic uptake of these tracers in the pancreatic head - a common site of neuroendocrine tumor (NET) involvement. We present false positive uptake on Ga DOTATATE PET/CT along with false positive CT findings. Role of other imaging modalities is discussed. PATIENT CONCERNS: A 78-year-old woman presented with a year-long history of diarrhea. DIAGNOSIS: Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL (normal <75 pg/mL). CT showed a mildly enhancing 2.5 cm × 1.8 cm × 2.8 cm area in the pancreatic uncinate process which corresponded to focal uptake with Ga DOTATATE PET/CT. A presumptive diagnosis of pancreatic NET (vipoma) was made, and the patient was scheduled to undergo Whipple's surgery. INTERVENTIONS: She sought a second opinion and a subsequent magnetic resonance imaging (MRI) showed no lesion and the patient's surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. OUTCOMES: Patient is currently pursuing workup for alternative etiologies for chronic diarrhea. LESSONS: Conspicuous physiological uptake has been reported in the pancreatic head on 16% to 70% of Ga DOTATATE or Ga DOTANOC PET/CT scans, and 26% of the In octreotide scintigraphy scans. Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by MRI or EUS. Interestingly, the patient described also had mild contrast enhancement on CT, but without an MRI correlate. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care.

Life-threating diarrhea and acute renal failure secondary to pancreatic VIPoma treated by surgery.

Pancreatic neuroendocrine tumors represent less than 5% of all pancreatic tumors. They are a heterogeneous group of neoplasms with a diverse behavior and prognosis. Pancreatic vasoactive intestinal polypeptide tumor (VIPoma) is an exceptional tumor within this group due to its low incidence. The presence of pancreatic VIPoma should be clinically suspected in all patients with watery diarrhea, particularly when accompanied by a loss of potassium and bicarbonate and a pancreatic mass on imaging. There are other pathologies with similar symptoms; therefore, a correct differential diagnosis with an adequate treatment is essential for its management. We present the case of a 46-year-old patient who developed a prerenal kidney failure secondary to severe watery diarrhea after a diagnosis of pancreatic VIPoma. Thus, a resection was performed as the patient was rapidly deteriorating and required an intervention.

Imaging of Pancreatic-Neuroendocrine Tumours: An Outline of Conventional Radiological Techniques.

INTRODUCTION: Pancreatic Neuroendocrine Tumours (p-NETs) are an important disease entity and comprise of peptide-secreting tumours often with a functional syndrome. Accounting for a small percentage of all pancreatic tumours, they have a good overall survival rate when diagnosed early, with surgery being curative. The role of nuclear medicine in the diagnosis and treatment of these tumours is evident. However, the vast majority of patients will require extensive imaging in the form of conventional radiological techniques. It is important for clinicians to have a fundamental understanding of the p-NET appearances to aid prompt identification and to help direct management through neoplastic staging. METHODS: This article will review the advantages and disadvantages of conventional radiological techniques in the context of p-NETs and highlight features that these tumours exhibit. CONCLUSION: Pancreatic neuroendocrine tumours are a unique collection of neoplasms that have markedly disparate clinical features but similar imaging characteristics. Most p-NETs are small and welldefined with homogenous enhancement following contrast administration, although larger and less welldifferentiated tumours can demonstrate areas of necrosis and cystic architecture with heterogeneous enhancement characteristics. Prognosis is generally favourable for these tumours with various treatment options available. However, conventional radiological techniques will remain the foundation for the initial diagnosis and staging of these tumours, and a grasp of these modalities is extremely important for physicians.

Pancreatic Neuroendocrine Tumor Secreting Vasoactive Intestinal Peptide and Dopamine With Pulmonary Emboli: A Case Report.

CONTEXT: The vasoactive intestinal peptide-secreting neuroendocrine tumor (VIPoma) is a very rare pancreatic tumor. We report the first case of a patient with VIPoma that co-secreted dopamine and had pulmonary emboli. CASE DESCRIPTION: A 67-year-old woman presented with 2 months of watery diarrhea, severe generalized weakness,6.8 kg of weight loss, a facial rash, and hypokalemia. Colonoscopy did not reveal the cause of the chronic diarrhea. Initial biochemical testing showed markedly elevated serum vasoactive intestinal peptide (VIP) and pancreatic polypeptide. Computed tomography scan of the abdomen and pelvis revealed a 5.4-cm distal pancreatic mass. Octreoscan showed an intense uptake in the area of the pancreatic mass. Incidental pulmonary emboli were found and treated. Additional biochemical testing revealed a markedly elevated urinary dopamine level. The patient received preoperative α-blockade and octreotide. She underwent a successful laparoscopic distal pancreatectomy. Postoperative urinary dopamine and pancreatic polypeptide were within normal limits. Serum VIP decreased by half but remained elevated. Pathology confirmed a grade 1 pancreatic neuroendocrine tumor without lymph node metastasis. The patient's symptoms resolved and no longer required octreotide. Metastatic workup including computed tomography, F18-fluorodeoxglucose positron emission tomography, and Ga68-DOTATATE scans were negative during 4 years of follow-up. CONCLUSIONS: VIPoma is a rare subtype of pancreatic neuroendocrine tumor that can secrete dopamine and can be associated with thromboembolism.

Role of endoscopic ultrasound in evaluation of pancreatic neuroendocrine tumors--report of 22 cases from a tertiary center in Iran.

BACKGROUND: The pancreatic neuroendocrine tumor (pNET) is relatively rare and generally felt to follow an indolent course. EUS has an important role in detection of pNET. This is a review of clinical and radiological presentation and pathologic reports of 22 patients with pNET. PATIENTS AND METHODS: In this study we analyzed clinical and radiological presentations and pathologic reports of all relevant cases who were referred to Taleghani hospital for 3 years since 2008. RESULTS: A total of 22 patients 28-74 years old (mean=49) were enrolled between 2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16 (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases but EUS was capable of detecting the lesions in these patients, cysts being found in 4 (19%) patients. CONCLUSION: EUS is a highly sensitive procedure for the localization of functional pNETs and especially insulinomas. Nonfunctional tumors were detected in more advanced and late stages and cystic lesions were more common in this group.

Pancreatic VIPomas: subject review and one institutional experience.

VIPomas are rare pancreatic endocrine tumors associated with a well-defined clinical syndrome characterized by watery diarrhea, hypokalemia, and metabolic acidosis. The objective of this study was to review a single institution's experience with VIPomas, as well as to review the English literature. A retrospective review of the Johns Hopkins pancreatic database revealed four cases of VIPoma, with three patients being male. All patients presented with watery diarrhea, hypokalemia, hypercalcemia, and acidosis. All patients had no family history of multiple endocrine neoplasia. Computed tomography revealed the primary pancreatic tumor in all patients, with three tumors located in the tail of the pancreas. One tumor involved the entire pancreas. Computed tomography and/or octreotide radionuclide scans identified hepatic metastasis in three patients. Mean serum vasoactive intestinal polypeptide levels were 683 pg/ml (range 293 to 1,500 pg/ml). All patients underwent resection of the pancreatic primary tumor. Two patients also had simultaneous liver resections. All patients had evidence of malignancy as defined by the presence of metastatic lymph nodes and/or hepatic metastases. Two patients had complete resolution of symptoms after surgical resection. One patient required radioablation of liver metastases and adjuvant octreotide therapy for control of symptoms. One patient died of progressive metastatic disease 96 months after surgery, whereas the other three remain alive. Extended, meaningful survival can be achieved for VIPoma patients, combining an aggressive surgical approach with additional strategies for treatment of unresected disease.

[Diagnostic procedures and more particularly, place of scintigraphy in neuroendocrine tumors, example of vipoma in MEN 1]. / Outils diagnostiques et plus particulièrement, place de la scintigraphie dans les tumeurs neuroendocrines: l'exemple d'un vipome dans une NEM de type 1.

Functioning endocrine pancreatic tumors in multiple endocrine neoplasia type 1 (MEN1) are rare. We present a case of a symptomatic neuroendocrine tumor in a 27-year old woman. The identification of the nature of the neuroendocrine tumors was difficult despite the use of a wide range of diagnostic procedures. This case is interesting in many ways: this is an exceptional illustration of MEN 1 with vipoma associated with calcitonin secretion and it is also a good example of the benefits and limitations of each diagnostic procedure in the heterogeneous group of neuroendocrine tumors.

Diagnosis and treatment of VIPoma in a female patient.

We report a case of VIPoma in an 83-year-old female patient, who presented with frequent and excessive diarrhoea, muscle weakness, and severe hypokalaemia. Abdominal computed tomography (CT) revealed a 4x6 cm mass in the body of the pancreas. Laboratory analysis showed elevated levels of both vasoactive intestinal polypeptide (VIP; 153 pmol/l) and pancreatic polypeptide (161 pmol/l). In view of the patient's age, physical condition, and tumour size, surgical resection was not performed. The patient was treated with a long-acting octreotide, after which her symptoms diminished. After 24 months of follow-up, the patient remained in good physical condition without any further serious gastrointestinal symptoms. The VIPoma syndrome is caused by a neuroendocrine tumour, usually located in the pancreas, which secretes VIP, causing severe diarrhoea, dehydration and hypokalaemia. Treatment options include resection of the tumour, chemotherapy or the reduction of symptoms with somatostatin analogues. We provide an overview of the incidence, pathophysiology, diagnosis, treatment strategies, and prognosis of this rare syndrome.

Laparoscopic distal pancreatectomy for neuroendocrine tumors of the pancreas.

Although neuroendocrine tumors of the pancreas are traditionally managed by laparotomy, these rare neoplasms may be amenable to laparoscopic surgical resection. We present our experience with laparoscopic distal pancreatectomy in two such patients, and discuss the operative technique with emphasis on organ preservation. Two female patients aged 63 and 69 years presented with clinical and biochemical features of an insulinoma and a vasoactive intestinal peptide secreting tumor (VIPoma), and were found on cross-sectional imaging to have 1.2-cm and 4.5-cm solitary tumors in the tail of the pancreas. They underwent laparoscopic distal pancreatectomy with and without preservation of splenic vessels and spleen respectively. Both procedures were completed laparoscopically. The operating time was 180 and 210 minutes respectively. There were no postoperative complications. The postoperative hospital stay was 4 and 14 days respectively. Histology revealed a benign insulinoma and a malignant VIPoma with lymph node metastases respectively. Laparoscopic distal pancreatectomy for neuroendocrine tumors of the pancreas may be accomplished safely, with preservation of the spleen and splenic vessels in benign disease, and with benefits to the patients in terms of postoperative recovery.

[Sonographic detection of a "VIPoma" in a small child with intractable gastroenteritis]. / Sonographische Detektion eines "VIPoms" bei einem Kleinkind mit therapieresistenter Gastroenteritis.

As case report we describe a rare cause of intractable "gastroenteritis" detected by ultrasonography. The 14 months-old boy was admitted to hospital because of intensive dehydration due to massive vomiting and diarrhoea. A salmonella enteritis with intractable hyponatraemia and hypokalaemia was thought to be the cause. After a dramatic relapse during oral treatment measures, further extensive laboratory tests finally disclosed an elevated serum level of vasoactive intestinal polypeptide ("VIP"). The VIP secreting tumor ("VIPoma") was detected ultrasonographically in a retroperitoneal localization mediocaudally of the right kidney. Diffuse distinct calcifications and an increased perfusion could be demonstrated. Intraspinal tumour spread was excluded by magnetic resonance imaging. After complete surgical removal of the tumour the clinical symptomatology normalized promptly and permanently. A VIP-excreting ganglioneuroblastoma with low grade growth fraction ("VIPoma") was diagnosed histologically. Common gastroenteritis in childhood represents no indication for ultrasound. In cases of unclear and therapy-resistant symptomatology, however, diagnostic work-up should include ultrasonography to search for retroperitoneal or pancreatic VIP-excreting tumours.

Surgical treatment of pancreatic vasoactive intestinal polypeptide-secreting tumor: a case report.

A 68-year-old woman presented with secretory watery diarrhea causing hypokalimia, hypoalbuminemia and dehydration for 5 years. Subsequent investigations including abdominal ultrasonography and computed tomography scanning revealed a mass measuring 7 x 6 cm in the pancreatic tail. The diagnosis of pancreatic VIPomas was suspected on the basis of clinical symptoms. The patient underwent distal pancreatectomy and splenectomy after resuscitation of electrolyte imbalance, dehydration and malnutrition. The pathological examination with histoimmunochemical stain confirmed the diagnosis. Postoperative course is uneventful and the patient does not have symptoms any longer during the follow-up period.

Metastatic jejunal VIPoma: beneficial effect of combination therapy with interferon-alpha and 5-fluorouracil.

The VIPoma syndrome is rare. It is usually caused by a neuroendocrine tumor located in the pancreas. Somatostatin analogs and interferon-a can be helpful in the symptomatic control of the disease, but the efficacy of chemotherapy in metastatic disease is limited. We report the case of a 32-yr-old patient who had a primary intestinal VIPoma with peritoneal carcinomatosis and hepatic metastases. Somatostatin analogs and conventional chemotherapy regimens were not effective on VIPoma syndrome and tumor progression. The combination of 5- fluorouracil and interferon-alpha was associated with a major clinical improvement and tumor regression. Further investigations should evaluate the place of such a combination as a first line treatment for patients with metastatic neuroendocrine tumors.

Location of a VIPoma by iodine-123-vasoactive intestinal peptide scintigraphy.

A major problem in patients with small endocrine tumors is the difficulty in localizing the primary tumor site. Many endocrine tumors possess larger amounts of high affinity vasoactive intestinal peptide (VIP) binding sites compared with normal tissue or blood cells. We used radiolabeled VIP to localize the tumor site in a patient with Verner-Morrison syndrome (VMS). Under octreotide therapy, the VIP levels had declined in this patient, but a tumor site could not be detected by conventional techniques or by radiolabeled octreotide. However, using 123I-VIP, the tumor was detectable in the pancreatic tail. Surgical resection of the tumor was followed by complete remission of the VMS. Expression of VIP binding sites in the tumor was confirmed by a radioreceptor assay and showed cross-competition between VIP and octreotide. The identity of the VIP binding site in the tumor was analyzed by Northern blotting and revealed the expression of somatostatin receptor subtype 3, which binds both somatostatin-14 and VIP with higher affinity than octreotide. Iodine-123-VIP scintigraphy would be an effective tracer to identity the tumor site in VMS patients.

Preliminary evaluation of the usefulness of Tc-99m (V) DMSA in pancreatic neuroendocrine tumors.

The authors describe the possible application of Tc-99m (V) DMSA scintigraphy in pancreatic neuroendocrine tumors. In consideration of the common embryonic origin of these tumors and other neoplastic diseases (medullary thyroid carcinoma, pheocromocytoma, neuroblastoma) that have been well studied with radionuclide imaging, five cases of pancreatic neuroendocrine tumors (two insulinomas, one vipoma, and two unclassified neuroendocrine tumors) were successfully visualized with Tc-99m (V) DMSA scintigraphy, thus giving an overall "imaging confirmation" of the histologic and/or cytologic results in terms of primary and metastatic localization. The authors point out the importance of their results, obtained in a simple and repeatable manner, and suggest a real comparison in this setting between this approach and octreotide scintigraphy.

111In-pentetreotide (somatostatin analogue) scintigraphy as an imaging procedure for endocrine gastro-entero-pancreatic tumors.

It was the aim of the present study to examine whether 111In-pentetreotide, a somatostatin analogue with predominantly renal excretion, is a suitable receptor agonist for scintigraphic imaging of endocrine gastro-entero-pancreatic (GEP) tumors, and to evaluate the contribution of the usual imaging times 4 and 24 h p.i. In 36 patients, planar scintigrams obtained 4 h, and 24 h after i.v. injection of 111 or 222 MBq 111In-pentetreotide were compared to the results of other imaging procedures and of surgery. Single photon emission computed tomography (SPECT) was also performed 24 h p.i. Positive scintigraphies were obtained in 32 out of 36 patients (18/19 patients with carcinoid syndrome, 8/9 with non hormone-producing endocrine GEP tumors, 2/4 with gastrinomas, 1/1 with glucagonoma, 1/1 with a VIPoma, 2/2 with paragangliomas). In 9 patients tumor manifestations previously not detected by conventional imaging procedures were disclosed by 111In-pentetreotide scintigraphy. 24-h images yielded significantly more true positive findings than 4-h images. In 4 patients liver metastases missed on planar scans were detected by SPECT. A discrepancy between patient-based and organ-based analysis of the results was encountered thus indicating a possible intraindividual heterogeneity in somatostatin receptor expression. In conclusion, 111In-pentetreotide is a suitable somatostatin analogue for scintigraphic in vivo demonstration of somatostatin receptors and for imaging of most tumor manifestations in patients with endocrine GEP tumors. Further studies will have to evaluate whether or not a positive receptor scintigraphy predicts response to treatment with long-acting somatostatin analogues.

Tc-99m sestamibi imaging of a pancreatic VIPoma and parathyroid adenoma in a patient with multiple type I endocrine neoplasia.

Technetium-99m sestamibi is known to localize in primary malignant and metastatic tumors. Specifically, brain, breast, thyroid, parathyroid, lung, and kidney tumors have been imaged. The Verner Morrison syndrome, which is caused by excessive vasoactive intestinal peptide (VIP), consists of watery diarrhea, hypokalemia, and achlorhydria. This condition is rarely associated with multiple endocrine neoplasia. The authors present a case of multiple endocrine neoplasia type I with visualization of a pancreatic VIPoma and parathyroid adenoma with Tc-99m MIBI.